Consolidation of a Molecular Signature of Healing in Cutaneous Leishmaniasis Is Achieved during the First 10 Days of Treatment.

The immune response is central to the pathogenesis of cutaneous leishmaniasis (CL). However, most of our current understanding of the immune response in human CL derives from the analysis of systemic responses, which only partially reflect what occurs in the skin. In this study, we characterized the transcriptional dynamics of skin lesions during the course of treatment of CL patients and identified gene signatures and pathways associated with healing and nonhealing responses. We performed a comparative transcriptome profiling of serial skin lesion biopsies obtained before, in the middle, and at the end of treatment of CL patients (eight who were cured and eight with treatment failure). Lesion transcriptomes from patients who healed revealed recovery of the stratum corneum, suppression of the T cell-mediated inflammatory response, and damping of neutrophil activation, as early as 10 d after initiation of treatment. These transcriptional programs of healing were consolidated before lesion re-epithelization. In stark contrast, downregulation of genes involved in keratinization was observed throughout treatment in patients who did not heal, indicating that in addition to uncontrolled inflammation, treatment failure of CL is mediated by impaired mechanisms of wound healing. This work provides insights into the factors that contribute to the effective resolution of skin lesions caused by Leishmania (Viannia) species, sheds light on the consolidation of transcriptional programs of healing and nonhealing responses before the clinically apparent resolution of skin lesions, and identifies inflammatory and wound healing targets for host-directed therapies for CL.

[Start of enteral nutrition after an endoscopic gastrostomy, is it necessary to wait?] / Inicio de nutrición enteral luego de una gastrostomía endoscópica, ¿es necesario esperar?

Traditionally, the initiation of enteral nutrition after a percutaneous endoscopic gastrostomy (PEG) is performed between 12 and 24 hours. Different research suggests that early initiation might be a safe option. Our aim was to determine whether starting enteral nutrition 4 hours after performing PEG is a safe practice in terms of risk of intolerance, complications, or death, compared to starting it at 12 hours. We carried out a prospective, randomized, multicenter study in third and fourth level institutions in Bogotá and Cundinamarca, between June 2020 and May 2022, 117 patients were included who were randomized into 2 groups, group A with early nutrition initiation (4 hours), and standard group B (12 hours). The most frequent mechanism of dysphagia was cerebrovascular disease (43%), followed by complications of COVID19 infection (26%). There were no statistically significant differences between the groups evaluated regarding the percentage of intolerance to nutrition, RR = 0.93 (CI 0.30-2.90), there were also no differences in terms of postoperative complications, (RR) = 0.34 (CI 0.09-1.16), and no differences were found in mortality between the evaluated groups, (RR) = 1.12 (CI 0.59-2.15). In conclusion, early initiation of nutrition through the gastrostomy, 4 hours after performing the PEG, is a safe behavior that is not related to greater intolerance to nutrition, complications, or death, compared to later initiation.

Immuno-pharmacokinetics of Meglumine Antimoniate in Patients With Cutaneous Leishmaniasis Caused by Leishmania (Viannia).

BACKGROUND: Control of cutaneous leishmaniasis (CL) relies on chemotherapy, yet gaps in our understanding of the determinants of therapeutic outcome impede optimization of antileishmanial drug regimens. Pharmacodynamic (PD) parameters of antimicrobials are based on the relationship between drug concentrations/exposure and microbial kill. However, viable Leishmania persist in a high proportion of individuals despite clinical resolution, indicating that determinants other than parasite clearance are involved in drug efficacy. METHODS: In this study, the profiles of expression of neutrophils, monocytes, Th1 and Th17 gene signatures were characterized in peripheral blood mononuclear cells (PBMCs) during treatment with meglumine antimoniate (MA) and clinical cure of human CL caused by Leishmania (Viannia). We explored relationships of immune gene expression with plasma and intracellular antimony (Sb) concentrations. RESULTS: Our findings show a rapid and orchestrated modulation of gene expression networks upon exposure to MA. We report nonlinear pharmacokinetic/pharmacodynamic (PK/PD) relationships of Sb and gene expression dynamics in PBMCs , concurring with a time lag in the detection of intracellular drug concentrations and with PK evidence of intracellular Sb accumulation. CONCLUSIONS: Our results quantitatively portray the immune dynamics of therapeutic healing, and provide the knowledge base for optimization of antimonial drug treatments, guiding the selection and/or design of targeted drug delivery systems and strategies for targeted immunomodulation.

The effect of comorbidities on glycemic control among Colombian adults with diabetes mellitus: a longitudinal approach with real-world data.

BACKGROUND: Achieving an optimal glycemic control has been described to reduce the incidence of diabetes mellitus (DM) related complications. The association between comorbidities and glycemic control remains unclear. Our aim is to evaluate the effect of comorbidities on glycemic control in people living with DM. METHODS: A retrospective longitudinal study on data from the National Registry of Chronic Kidney Disease from 2014 to 2019 in Colombia. The outcome was poor glycemic control (PGC = HbA1c ≥7.0%). The association between each comorbidity (hypertension (HTN), chronic kidney disease (CKD) or obesity) and PGC was evaluated through multivariate mixed effects logistic regression models. The measures of effect were odds ratios (OR) and their 95% confidence intervals (CI). We also evaluated the main associations stratified by gender, insurance, and early onset diabetes as well as statistical interaction between each comorbidity and ethnicity. RESULTS: From 969,531 people at baseline, 85% had at least one comorbidity; they were older and mostly female. In people living with DM and CKD, the odds of having a PGC were 78% (OR: 1.78, CI 95%: 1.55-2.05) higher than those without CKD. Same pattern was observed in obese for whom the odds were 52% (OR: 1.52, CI 95%: 1.31-1.75) higher than in non-obese. Non-significant association was found between HTN and PGC. We found statistical interaction between comorbidities and ethnicity (afro descendant) as well as effect modification by health insurance and early onset DM. CONCLUSIONS: Prevalence of comorbidities was high in adults living with DM. Patients with concomitant CKD or obesity had significantly higher odds of having a PGC.

Phenotypic and functional stability of leukocytes from human peripheral blood samples: considerations for the design of immunological studies.

BACKGROUND: Human peripheral blood mononuclear cells (PBMCs) are extensively used for research of immune cell functions, identification of biomarkers and development of diagnostics and therapeutics for human diseases, among others. The assumption that "old blood samples" are not appropriate for isolation of PBMCs for functional assays has been a dogma in the scientific community. However, partial data on the impact of time after phlebotomy on the quality and stability of human PBMCs preparations impairs the design of studies in which time-controlled blood sampling is challenging such as field studies involving multiple sampling centers/sites. In this study, we evaluated the effect of time after phlebotomy over a 24 h time course, on the stability of human blood leukocytes used for immunological analyses. Blood samples from eight healthy adult volunteers were obtained and divided into four aliquots, each of which was left in gentle agitation at room temperature (24 °C) for 2 h (control), 7 h, 12 h and 24 h post phlebotomy. All samples at each time point were independently processed for quantification of mononuclear cell subpopulations, cellular viability, gene expression and cytokine secretion. RESULTS: A 24 h time delay in blood sample processing did not affect the viability of PBMCs. However, a significantly lower frequency of CD3+ T cells (p < 0.05) and increased LPS-induced CXCL10 secretion were observed at 12 h post-phlebotomy. Alterations in TNFα, CCL8, CCR2 and CXCL10 gene expression were found as early as 7 h after blood sample procurement. CONCLUSIONS: These data reveal previously unrecognized early time-points for sample processing control, and provide an assay-specific time reference for the design of studies that involve immunological analyses of human blood samples.

Urological approach for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a clinical care center.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is associated with significant manipulation of the urinary tract (UT). We aim to describe the urological events and their management in patients who underwent CRS-HIPEC. METHODS: Clinical records of patients who underwent treatment between 2007 and 2015 were reviewed. Urological events and their multidisciplinary management were analyzed. Descriptive statistics were calculated. RESULTS: A total of 103 patients were included. Mean age was 51 years (SD ± 11.8). Mean peritoneal cancer index (PCI) was 20.4 (SD ± 10.1). Primary tumors included appendicular (64%), gynecological (16%), colorectal (10%), and peritoneal mesotheliomas (9%). Ninety-three percent of patients had bilateral ureteral catheters inserted prior to surgery, without complications. Intraoperative UT injuries occurred in 7% of patients. In 5% of patients, tumor invasion of the bladder was evident at surgery and partial resection and primary repair of the bladder wall was performed. Urological complications included urinary tract infection (UTI) (21%) acute post-renal failure (4%), urinary fistulae (4%), and acute urinary retention (AUR) (1%). CONCLUSIONS: In our study, intraoperative UT events and postoperative complications, although not neglectable, were infrequent. Due to the high complexity of these cases, a multidisciplinary approach is mandatory. However, randomized clinical trials are necessary to clarify current data on the need and efficacy of prophylactic ureteral catheterization in patients undergoing CRS-HIPEC.

Diagnostic approach and monitoring of chronic kidney disease in the primary care pediatric population.

Chronic kidney disease (CKD) has severe consequences on the quality and expectancy of life and is considered a major health problem worldwide. This is, especially relevant in pediatric patients, as they have unique characteristics and a mortality rate 30 times higher (in advanced stages) than healthy people. This review aims to define the minimum components for the diagnostic approach and monitoring of CKD in the pediatric population from primary health care to promote comprehensive care and adequate risk management. For this purpose, we performed a systematic review of the literature with a panel of experts. Based on the evidence, to optimize the definition, diagnosis, and timely treatment of CKD in the pediatric population, we formulated 21 recommendations. These were approved by the research team and peer-reviewed by clinical experts. They will facilitate the definition of the diagnostic approach for CKD in the pediatric population in primary health-care settings, allowing for timely treatment intervention, comprehensive care, and monitoring of this disease.

La enfermedad renal crónica (ERC) tiene graves consecuencias en la calidad y la esperanza de vida, y se considera un importante problema de salud a nivel mundial. Esto es especialmente relevante en pacientes pediátricos, ya que presenta características únicas y una tasa de mortalidad en etapas avanzadas que es 30 veces mayor que en personas sanas. El objetivo de esta revisión fue definir los componentes mínimos para el abordaje diagnóstico y para el seguimiento de la ERC en la población pediátrica desde la atención primaria en salud, con el fin de promover la atención integral y una adecuada gestión del riesgo. Para esto, se realizó una revisión sistemática de la literatura con panel de discusión de expertos. Basándonos en la evidencia, y con el objetivo de optimizar la definición, diagnóstico y tratamiento oportuno de la ERC en la población pediátrica, se formularon 21 recomendaciones. Estas fueron aprobadas por el equipo desarrollador y los pares expertos clínicos evaluadores, y permitirán definir de manera oportuna el abordaje diagnóstico de la ERC en la población pediátrica desde la atención primaria en salud, facilitando la intervención temprana, una atención integral y el seguimiento de esta patología.

Innate biosignature of treatment failure in human cutaneous leishmaniasis.

The quality and magnitude of the immune and inflammatory responses determine the clinical outcome of Leishmania infection, and contribute to the efficacy of antileishmanial treatments. However, the precise immune mechanisms involved in healing or in chronic immunopathology of human cutaneous leishmaniasis (CL) are not completely understood. Through sequential transcriptomic profiling of blood monocytes (Mo), neutrophils (Nφ), and eosinophils (Eφ) over the course of systemic treatment with meglumine antimoniate, we discovered that a heightened and sustained Type I interferon (IFN) response signature is a hallmark of treatment failure (TF) in CL patients. The transcriptomes of pre-treatment, mid-treatment and end-of-treatment samples were interrogated to identify predictive and prognostic biomarkers of TF. A composite score derived from the expression of 9 differentially expressed genes (common between Mo, Nφ and Eφ) was predictive of TF in this patient cohort for biomarker discovery. Similarly, machine learning models constructed using data from pre-treatment as well as post-treatment samples, accurately classified treatment outcome between cure and TF. Results from this study instigate the evaluation of Type-I IFN responses as new immunological targets for host-directed therapies for treatment of CL, and highlight the feasibility of using transcriptional signatures as predictive biomarkers of outcome for therapeutic decision making.

MDRD is the eGFR equation most strongly associated with 4-year mortality among patients with diabetes in Colombia.

INTRODUCTION: We compared the association of glomerular filtration rate (GFR) estimated with the Cockcroft-Gault, Modification of Diet in Renal Disease study (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or the new CKD-EPI without race (CKD-EPI-NR) equations, with 4-year all-cause mortality in patients with diabetes. RESEARCH DESIGN AND METHODS: We analyzed a nationwide, centralized database of all adults diagnosed with diabetes assisted by the Colombian Health System between July 1, 2015, and June 30, 2019. Plasma creatinine was used to calculate baseline estimated glomerular filtration rate (eGFR) and classify each patient in a chronic kidney disease (CKD) stage, by each of the four equations. We used multivariate logistic regression to compare the association between CKD stage and mortality, and receiver operating characteristic (ROC) analyses to assess the overall association of eGFR by each equation and mortality. RESULTS: The study included 758,219 patients (58% female, 7.2% black race, mean age 62.3, Glycated hemoglobin A1c [HbA1c] 7.4%). There were 35,296 deaths over the study follow-up. Considering eGFR by each equation as a continuous variable, the odds of death decreased by 1.1%-1.5% for each additional mL/min. Compared with CKD stage 1 of each equation, being placed in CKD stages 3a, 3b, or 4 by MDRD or CKD-EPI-NR was associated with greater odds of death than being categorized in the same stages by CKD-EPI. Among patients of black race, the adjusted OR of mortality for CKD stage 4 relative to stage 1 was 4.63 (95% CI 3.39 to 6.35) for MDRD, 3.66 (2.85 to 4.69) for CKD-EPI-NR, 3.01 (2.38 to 3.81) for CKD-EPI, and 2.82 (2.29 to 3.49) for Cockcroft-Gault. The area under the ROC curve to discriminate by survival status was greatest for MDRD, followed by CKD-EPI-NR, CKD-EPI, and Cockcroft-Gault, in that order (p<0.001 for all differences). CONCLUSIONS: Compared with other eGFR equations, MDRD showed the strongest association with all-cause mortality in a sample of Latin-American patients with diabetes. This difference was most pronounced among patients of black race.

Impact of metabolic control on all-cause mortality in a nationwide cohort of patients with diabetes from Colombia.

Objective: The magnitude of the mortality benefit conferred by good integral metabolic control in diabetes in not sufficiently known, especially among Latin American patients. We prospectively studied the association between sustained control of blood glucose (HbA1c<7%), systolic blood pressure (SBP) (<130 mmHg) and LDL (LDLc, <100mg/dL) and non-HDL (non-HDLc, <130 mg/dL) cholesterol, and death from any cause among all adult patients with diagnosed diabetes in Colombia. Methods: We retrospectively analyzed data from a nationwide, centralized, mandatory registry of all patients with diagnosed diabetes assisted by the Colombian health system between July 1, 2015, and June 30, 2019. We estimated the associations of sustained achievement of each goal, and of the joint triple goal (HbA1c + SBP + LDLc) with all-cause death. Associations were assessed after adjustment for sex, age, race, insurance type and BMI in multivariable logistic models. Results: We studied 1 352 846 people with diabetes. Sustained SBP (OR 0.42 [0.41-0.43]), HbA1c (OR 0.25 [0.24-0.26]) and LDLc (OR 0.28 [0.27-0.29]) control had strong negative associations with death. Moreover, among the 5.4% of participants who achieved joint, sustained metabolic control, the OR for death was 0.19 (0.18-0.21). Importantly, the impact of sustained, joint metabolic control was significantly smaller for patients of black race compared to other races (OR 0.31 [0.23-0.43] versus 0.18 [0.17-0.20], p-value for interaction <0.001), mostly at the expense of a smaller impact of LDLc control. The results were similar across body-mass index categories. Conclusions: Sustained and simultaneous metabolic control was associated with remarkably lower odds of death.

Strong Negative Association of non-HDL Cholesterol Goal Achievement With Incident CKD Among Adults With Diabetes.

Context: The relative importance of the control of different metabolic risk factors for the prevention of chronic kidney disease among patients with diabetes in real life conditions is insufficiently understood. Objective: We evaluated the effect of the achievement of glycated hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDLc) or non-high-density lipoprotein cholesterol (non-HDLc) goals (ABC goals) on the development of incident chronic kidney disease (iCKD) among patients with diabetes. Methods: In a nationwide registry of all individuals diagnosed with diabetes assisted by the health system in Colombia, we analyzed the association between baseline or sustained goal achievement and development of iCKD over a 4-year follow-up. iCKD was defined as a new occurrence of an estimated glomerular filtration rate less than 60 mL/min/1.73 m2, hemodialysis, peritoneal dialysis, or kidney transplant. Results: The study included 998 790 adults with diabetes (56% female, mean age 59). There were 125 626 cases of iCKD. After adjustment for multiple confounders, a baseline SBP less than 130 mm Hg (odds ratio [OR] 0.79 [0.78-0.80]) and a baseline HbA1c less than 7.0% (OR 0.86 [0.85-0.87]) were negatively associated with iCKD. Sustained achievement showed stronger negative associations with iCKD than just baseline achievement. Considering each goal separately, sustained non-HDLc less than 130 mg/dL had the strongest negative association with iCKD (OR 0.67 [0.65-0.69]). Patients who maintained the triple ABC goal over the entire follow-up had 32% (29-34) lower odds of developing CKD, 38% (34-42) if they additionally kept a normal body mass index (BMI). Sustained ABC control including a normal BMI was more strongly associated with a lower incidence of CKD in patients of Black race (OR 0.72 vs 0.89; P for interaction = .002). Conclusion: At the country level, sustained achievement of ABC goals and most especially non-HDLc were associated with substantial reductions in iCKD.

Factors associated with coronary artery disease among people living with human immunodeficiency virus: Results from the Colombian HIV/AIDS registry.

Background: People living with HIV (PLWHIV) are at a higher risk of developing coronary artery disease (CAD). We aimed to assess the factors associated with CAD among PLWHIV in Colombia. Methods: We conducted a retrospective cohort study based on adults newly diagnosed with HIV, reported to the Colombian HIV/AIDS registry from 2018 to 2021. Baseline demographic and clinical characteristics were compared by age (<50 and ≥ 50 years). Our main outcome was the presence of CAD. Logistic regression models were used to assess the association between traditional and HIV-related factors with CAD. These associations were also evaluated in stratified models by age. Effect measures were odds ratios (OR) and their 95% confidence intervals. Results: Among 36,483 PLWHIV, the frequency of CAD was 0.53% (n = 196). There was a high prevalence of impaired fasting glucose/diabetes mellitus (12.62%), overweight/obesity (27.79%), elevated LDL-c (86.69%), and hypertriglyceridemia (72.76%). Factors associated with CAD included male gender (OR: 2.01, 95% CI: 1.12-3.58), age ≥50 years (OR: 4.96, 95% CI: 3.29-7.45), lipoatrophy or lipodystrophy (OR 5.12, 95% CI: 1.12-23.33), AIDS-defining conditions (OR: 1.83, 95% CI: 1.07-3.12), obesity (OR: 2.95, 95% CI: 1.69-5.10), diabetes mellitus (OR: 2.50, 95% CI: 1.25-4.97), and renal impairment (OR: 3.15, 95% CI: 1.83-5.42). Conclusions: Traditional CAD risk factors are common in PLWHIV. There were traditional and disease-specific factors associated with increased odds of CAD. These findings may aid clinicians and decision-makers in reducing the impact of CAD in PLWHIV.

Epidemiology of Clostridioides difficile infection in hospitalized patients in Spain: An eight-year review (2012-2019).

BACKGROUND: Clostridioides difficile infection (CDI) is a disease that is potentially preventable by vaccination. A good knowledge of its epidemiology, which can change over time, is warranted for prevention purposes and to help decision-making on the use of vaccines in public health programs. The objective of the research was to determine the epidemiology of healthcare-associated CDI (HA-CDI) and community-associated CDI (CA-CDI) in hospitalized patients in Spain using point prevalence data. METHODS: Point prevalence survey data on infections of hospitalized patients for years 2012-2019 were analyzed. HA-CDI and CA-CDI prevalence rates were calculated. Both HA-CDI and CA-CDI, as well as age group prevalence rates, were examined for trends. Patient comorbidities were tested for association to CDI. RESULTS: The prevalence of CDI in Spanish hospitals has grown exponentially from 14.1% in 2012 to 35.9% in 2019 (cases/10.000 hospitalized patients). Almost two thirds of the cases are of nosocomial onset. This increase was observed for HA-CDI and CA-CDI at an annual rate of 1.11% (CI 95% 1.08-1.15) and 1.09% (CI 95% 1.04-1.13), respectively. Patients 50 years old or older represent 87% of the total number of cases. Patients suffering from neoplasm (OR 1.39), immunodeficiency (OR 3.26), neutropenia (OR 3.70), cirrhosis (OR 1.92) and chronic renal failure (OR 1.91) have a significant increased risk of developing CDI, after adjusting for age. CONCLUSION: In Spain, the prevalence rate of both HA-CDI and CA-CDI have been increasing. Burden of CDI as well as clinical and epidemiological characteristics of CDI patients will help to support public health decision-making.

SARS-COV-2 seroprevalence among all healthcare workers in a tertiary hospital in Spain.

BACKGROUND: Healthcare workers (HCWs) have been a critical and vulnerable population during SARS-CoV-2 pandemic. The aim of this study was to determine the overall seroprevalence and to evaluate occupational risk factors among HCWs in one of the countries most affected by this pandemic. METHODS: We conducted a seroprevalence study for SARS-CoV-2 in a tertiary hospital in Madrid (Spain) between 24 April and 8 May 2020. A total of 4894 HCWs were invited for serologic testing. Serum samples were tested for SARS-CoV-2 IgM and IgG antibodies using Enzyme Immunoassay (ELISA) and Electro-Chemiluminescence Immunoassay (ECLIA) techniques. We calculated odds ratios to assess association between demographic and occupational characteristics with SARS-CoV-2 seroconversion. RESULTS: We processed 4324 serum samples. Overall, seroprevalence was of 16.6% (95% CI: 15.5-17.7). We found statistically significant differences in SARS-CoV-2 seroprevalence by type of employee, professional category, department and type of activity performed during the pandemic period, while no differences were identified between the personnel working in the COVID-19 wards compared to those working in non-COVID-19 wards. We confirmed 268 (26.7%) infections among 1005 hospital staff members tested by PCR. 60.5% of HCWs infected by SARS-CoV-2, assessed either by PCR or serology, could be considered asymptomatic or paucisymptomatic. CONCLUSIONS: HCWs have an increased risk of SARS-CoV-2 infection but COVID-19 patient exposure was not a determining factor. Universal mask wearing should be mandatory in healthcare settings given the important number of asymptomatic and paucisymptomatic cases.

Quality parameters for RNA preparations from biopsies of ulcerated human skin.

Background: Obtaining high quality RNA from skin biopsies is complex due the physical composition and high content of nucleases of this tissue. This becomes particularly challenging when using compromised skin samples with necrotic, inflammed or damaged areas, such as those from patients suffering skin conditions, which affect more than 900 million people annually. We evaluated the impact of the biopsy size and tissue preservation method on the quality and quantity of RNA extracts. Methods: Skin lesion biopsies were obtained from patients with cutaneous leishmaniasis (CL). Biopsy specimens of 2 mm (n = 10) and 3 mm (n = 59) were preserved in Allprotect® reagent, and 4 mm biopsies in OCT (n = 54). Quality parameters were evaluated using Nanodrop and Bioanalyzer. The informativeness of the extracted samples for downstream analyses was evaluated using RT-qPCR and RNA-Seq. Results: The success rate, based on quality parameters of RNA extraction from tissue biopsies stored in OCT and 2 mm biopsies stored in Allprotect®, was 56% (30/54) and 30% (3/10), respectively. For 3 mm skin biopsies stored in Allprotect® was 93% (55/59). RNA preparations from 3 mm-Allprotect® biopsies had an average RIN of 7.2 ± 0.7, and their integrity was not impacted by sample storage time (up to 200 days at -20°C). RNA products were appropriate for qRT-PCR and RNA-seq. Based on these results, we propose a standardized method for RNA extraction from disrupted skin samples. This protocol was validated with lesion biopsies from CL patients (n = 30), having a success rate of 100%. Conclusions: Our results indicate that a biopsy size of 3 mm in diameter and preservation in Allprotect® for up to 200 days at -20°C, are best to obtain high quality RNA preparations from ulcerated skin lesion biopsy samples.

Epidemiology of Clostridioides difficile infection in hospitalized patients in Spain: An eight-year review (2012-2019).

BACKGROUND: Clostridioides difficile infection (CDI) is a disease that is potentially preventable by vaccination. A good knowledge of its epidemiology, which can change over time, is warranted for prevention purposes and to help decision-making on the use of vaccines in public health programs. The objective of the research was to determine the epidemiology of healthcare-associated CDI (HA-CDI) and community-associated CDI (CA-CDI) in hospitalized patients in Spain using point prevalence data. METHODS: Point prevalence survey data on infections of hospitalized patients for years 2012-2019 were analyzed. HA-CDI and CA-CDI prevalence rates were calculated. Both HA-CDI and CA-CDI, as well as age group prevalence rates, were examined for trends. Patient comorbidities were tested for association to CDI. RESULTS: The prevalence of CDI in Spanish hospitals has grown exponentially from 14.1% in 2012 to 35.9% in 2019 (cases/10.000 hospitalized patients). Almost two thirds of the cases are of nosocomial onset. This increase was observed for HA-CDI and CA-CDI at an annual rate of 1.11% (CI 95% 1.08-1.15) and 1.09% (CI 95% 1.04-1.13), respectively. Patients 50 years old or older represent 87% of the total number of cases. Patients suffering from neoplasm (OR 1.39), immunodeficiency (OR 3.26), neutropenia (OR 3.70), cirrhosis (OR 1.92) and chronic renal failure (OR 1.91) have a significant increased risk of developing CDI, after adjusting for age. CONCLUSION: In Spain, the prevalence rate of both HA-CDI and CA-CDI have been increasing. Burden of CDI as well as clinical and epidemiological characteristics of CDI patients will help to support public health decision-making.

Inductively coupled plasma mass spectrometry method for plasma and intracellular antimony quantification applied to pharmacokinetics of meglumine antimoniate.

Background: A high-throughput method using inductively coupled plasma mass spectrometry (ICP-MS) was developed and validated for the quantitative analysis of antimony in human plasma and peripheral blood mononuclear cells from patients with cutaneous leishmaniasis undergoing treatment with meglumine antimoniate. Materials & methods: Antimony was digested in clinical samples with 1% tetramethylammonium hydroxide/1% EDTA and indium was used as internal standard. Accuracy, precision and stability were evaluated. Conclusion: Taking the lower limit of quantitation to be the lowest validation concentration with precision and accuracy within 20%, the current assay was successfully validated from 25 to 10000 ng/ml for antimony in human plasma and peripheral blood mononuclear cells. This protocol will serve as a baseline for future analytical designs, aiming to provide a reference method to allow inter-study comparisons.

Lay abstract Cutaneous leishmaniasis is a disease caused by single-cell parasites in the genus Leishmania which results in painful skin ulcers and is spread by insect bites. Drugs containing antimony are the mainstay therapy for cutaneous leishmaniasis, but if and how the amount of these compounds in the cells can affect the success of the treatment, remains unknown. Validated methods to reliably measure these amounts in human cells are limited. Here we have developed a validated method that allows quantifying antimony in human plasma and peripheral blood cells from patients undergoing antileishmanial treatment. This protocol will serve as a baseline for future studies aiming to understand how antimonials work to treat leishmaniasis infections and how this therapy can be improved.

A systematic review and meta-analysis of risk factors associated with acquisition of waterborne healthcare-associated infection or colonization in high-risk units.

In this meta-analysis, central venous catheter exposure (pooled odds ratio, 8.02; 95% confidence interval [CI], 2.19-29.31; P < .01) in neonates and length of stay (standardized mean difference, 0.65; 95% CI, 0.26-1.05; P = .01) in an adult population were associated with acquisition of waterborne healthcare-associated infections or colonization in ICUs. The quality of evidence was low.

Hospital Readmissions of Discharged Patients with COVID-19.

OBJECTIVE: To analyse the rate of occurrence and the clinical variables associated with readmission of patients who had previously been discharged after admission for COVID-19. SETTING: University hospital in Madrid (Spain). PARTICIPANTS: Sixty-one patients (74% male) who presented COVID-19 were readmitted during the 3 weeks after discharge from hospital. INTERVENTIONS: Nested case-control study paired (1:1 ratio) by age, sex and period of admission. OUTCOME MEASURES: Rate of readmission rate of patients discharged after suffering COVID-19 and identification of the clinical variables associated with it. RESULTS: Out of 1368 patients who were discharged during the study period, 61 patients (4.4%) were readmitted. Immunocompromised patients (N=10.2%) were at increased risk for readmission (p=0.04). There was also a trend towards a higher probability of readmission in hypertensive patients (p=0.07). Cases had had a shorter hospital stay and a higher prevalence of fever during the 48 hours prior to discharge. There were no significant differences in oxygen levels measured at admission and discharge by pulse oximetry intra-subject or between the groups. Neutrophil-to-lymphocyte ratio at hospital admission tended to be higher in cases than in controls (p=0.06). Neither glucocorticoids nor anticoagulants prescribed at hospital discharge were associated with a lower readmission rate. Patients who were readmitted due to a thrombotic event (8 patients, 13.1%) presented a higher level of D-dimer at discharge of initial admission. CONCLUSION: The rate of readmission after discharge from hospital for COVID-19 was low. Immunocompromised patients and those presenting with fever during the 48 hours prior to discharge were at greater risk of readmission to hospital.

Comparative Assessment of DNA Targets and Amplification Methods for Leishmania (Viannia) Detection in Human Samples.

Multiple polymerase chain reaction (PCR)-based approaches have been developed for Leishmania detection in clinical and laboratory samples, and this diversity limits inter-study comparisons, meta-analyses, and generalization of findings. Towards harmonization of a molecular tool for detection of Leishmania (Viannia) for research purposes, we evaluated the concordance of 18SrDNA quantitative polymerase chain reaction (qPCR) and minicircle kinetoplastid DNA (mkDNA) PCR followed by Southern blot (PCR-SB) in in vitro infection systems and in lesion and mucosal swab samples from Colombian patients with cutaneous leishmaniasis caused by L. (Viannia). The lower limit of parasite detection of 18SrDNA qPCR and mkDNA PCR-SB was 10-1 promastigotes and one intracellular amastigote per reaction. From cutaneous lesions (n = 63), an almost perfect concordance was found between the methods (κ = 0.92, 95% CI: 0.82-1.00). Despite equal limits of detection, mkDNA PCR-SB was more efficient for parasite detection in mucosal samples than 18SrDNA qPCR or 18SrDNA digital droplet PCR. The high concordance, sensitivity, scaling potential, and feasibility of implementation of the 18SrDNA qPCR, support its selection as the L. (Viannia) in research laboratories, as a first step towards harmonization of research protocols in the region.